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Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung cancer in a Chinese population
Author(s) -
Hu Zhibin,
Miao Xiaoping,
Ma Hongxia,
Tan Wen,
Wang Xinru,
Lu Daru,
Wei Qingyi,
Lin Dongxin,
Shen Hongbing
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20746
Subject(s) - lung cancer , biology , lung cancer susceptibility , haplotype , allele , genotype , genetics , linkage disequilibrium , exon , population , untranslated region , heterozygote advantage , allele frequency , gene , cancer research , single nucleotide polymorphism , medicine , messenger rna , environmental health
p73 , a structural and functional homologue of p53 , shares some p53‐like tumor suppressor activity but also possesses oncogenic activity. Therefore, p73 plays an important role in modulating cell‐cycle control and apoptosis. A potentially functional dinucleotide polymorphism, G4C14‐to‐A4T14, has been identified in the 5′ untranslated region (UTR) of exon 2 of the p73 gene, which may theoretically form a stem‐loop structure and affect gene expression. To test the hypothesis that these 2 common variants play a role in lung cancer susceptibility, we conducted a case‐control study of 425 lung cancer patients and 588 cancer‐free controls frequency‐matched to the cases on age and sex in a Chinese population. The results showed that these 2 polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less common in the cases (0.225) than in the controls (0.287) ( p = 0.0018), suggesting that this AT haplotype was protective against lung cancer. Compared to the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk (adjusted OR: 0.45, 95% CI: 0.26–0.80 and OR: 0.70, 95% CI: 0.53–0.92, respectively). These results suggest that this p73 dinucleotide polymorphism may have a role in lung cancer susceptibility in our study population. Further studies are needed to elucidate potential functional relevance of the p73 AT variant allele. © 2004 Wiley‐Liss, Inc.